Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity.

TitleLong-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity.
Publication TypeJournal Article
Year of Publication2022
AuthorsBiswas, S, Rust, LN, Wettengel, JM, Yusova, S, Fischer, M, Carson, JN, Johnson, J, Wei, L, Thode, T, Kaadige, MR, Sharma, S, Agbaria, M, Bimber, BN, Tu, T, Protzer, U, Ploss, A, Smedley, JV, Golomb, G, Sacha, JB, Burwitz, BJ
JournalNat Commun
Volume13
Issue1
Pagination2995
Date Published2022 May 30
ISSN2041-1723
KeywordsAnimals, Antigens, Surface, Hepatitis B, Hepatitis B virus, Hepatitis B, Chronic, Humans, Liver Neoplasms, Macaca mulatta
Abstract

<p>Hepatitis B virus has infected a third of the world's population, and 296 million people are living with chronic infection. Chronic infection leads to progressive liver disease, including hepatocellular carcinoma and liver failure, and there remains no reliable curative therapy. These gaps in our understanding are due, in large part, to a paucity of animal models of HBV infection. Here, we show that rhesus macaques regularly clear acute HBV infection, similar to adult humans, but can develop long-term infection if immunosuppressed. Similar to patients, we longitudinally detected HBV DNA, HBV surface antigen, and HBV e antigen in the serum of experimentally infected animals. In addition, we discovered hallmarks of HBV infection in the liver, including RNA transcription, HBV core and HBV surface antigen translation, and covalently closed circular DNA biogenesis. This pre-clinical animal model will serve to accelerate emerging HBV curative therapies into the clinic.</p>

DOI10.1038/s41467-022-30593-0
Alternate JournalNat Commun
PubMed ID35637225
PubMed Central IDPMC9151762
Grant ListP51 OD011092 / OD / NIH HHS / United States
R01 AI157612 / AI / NIAID NIH HHS / United States
R21 AI108401 / AI / NIAID NIH HHS / United States
R01 AI129703 / AI / NIAID NIH HHS / United States
R01 AI138797 / AI / NIAID NIH HHS / United States
R01 AI153236 / AI / NIAID NIH HHS / United States
R01 AI144008 / AI / NIAID NIH HHS / United States